This proposal presents a four-year research career development award for Dr. Reza Yaesoubi, an Assistant Professor in the Department of Health Policy and Management at the Yale School of Public Health (YSPH). His proposal aims to address important policy questions to control the ongoing spread of multidrug-resistant tuberculosis (MDR-TB) strains, which are resistant to essential antibiotics included in the first-line TB treatment regimen. While global efforts to scale up the diagnosis and treatment of MDR-TB and confront the growing problem of drug resistance have been slow moving, the recent introduction of new tools to control the threat of MDR-TB offer promise to accelerate the response. These new tools include rapid diagnostic tests for drug resistance and the novel anti-TB drugs. This proposal describes a rigorous, model-based investigation to identify strategies that can maximize the beneficial impact of these novel tools for TB and MDR-TB control. To study the overall impact of different control policies on MDR-TB spread, the candidate will develop detailed mathematical and simulation models of TB epidemics and calibrate them using data from two high MDR-TB prevalence countries, Peru and The Republic of Moldova (Aim 1). The candidate will then use these models to i) identify cost-effective, adaptive policies which use updated epidemiological information to guide targeted screening for TB and MDR-TB (Aim 2); and ii) identify drug-introduction policies that maximize the societal benefits of novel anti-T drugs and regimens while minimizing the probability of the emergence of antibiotic resistance (Aim 3). The proposed work will be conducted under the co-mentorship of Dr. Ted Cohen, MD, MPH, DrPH, Associate Professor of Epidemiology of Microbial Diseases at YSPH, and Dr. A. David Paltiel, PhD, MBA, Professor of Public Health, and Health Policy and Management at YSPH, and will be done in collaboration with the Center for Interdisciplinary Research on AIDS, the Center for Infectious Disease Modeling at YSPH, and the Center for Communicable Disease Dynamics at the Harvard School of Public Health (HSPH).The candidate will also be advised by Dr. Marc Lipsitch, DPhill, Professor of Epidemiology at HSPH and Dr. Joshua Salomon, PhD, Professor of Global Health at HSPH. Dr. Yaesoubi's training goals are (1) to develop a solid understanding of the dynamics of infectious diseases and the biological mechanisms governing the emergence of resistant bacteria, in particular MDR-TB, (2) to become an expert in methods for modeling complex multi-agent systems and optimizing the overall performance of these systems through the efficient allocation of available resources, and (3) to improve his mentoring, management, and collaboration skills that are essential for his successful transition to independence. The candidate's long-term goal is to become an independent scientist developing and applying decision science techniques to improve policies for the management and eradication of infectious diseases.